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Context: Dipeptidyl peptidase IV (DPP-IV) inactivates the incretin hormone glucagon-like peptide. It can also affect the orexigenic hormone neuropeptide Y (NPY1–36) which is truncated by DPP-IV to NPY3–36, as a consequence NPY’s affinity changes from receptor Y1, which mediates the antilipolytic function of NPY, to other NPY receptors. Little is known whether DPP-IV inhibitors for the treatment of type 2 diabetic (T2DM) patients could influence these pathways. Aims: To investigate the in vitro effects of NPY with DPP-IV inhibition in isolated abdominal subcutaneous (AbdSc) adipocytes on fat metabolism, and assessment of NPY receptor and DPP-IV expression in adipose tissue (AT). Methods: Ex vivo human AT was taken from women undergoing elective surgery (body mass index: 27.5 (mean ± s.d.) ± 5 kg/m2, age: 43.7 ± 10 years, n = 36). Isolated AbdSc adipocytes were treated with human recombinant (rh)NPY (1–100 nM) with and without DPP-IV inhibitor (1 M); glycerol release and tissue distribution of DPP-IV, Y1 and Y5 messenger RNA (mRNA) were measured and compared between lean and obese subjects. Results and conclusion: rhNPY reduced glycerol release, an effect that was further enhanced by co-incubation with a DPP-IV inhibitor [control: 224 (mean ± s.e.) ± 37 μmol/l; NPY, 100 nM: 161 ± 27 μmol/l**; NPY 100 nM/DPP-IV inhibitor, 1 M: 127 ± 14 μmol/l**; **p < 0.01, n = 14]. DPP-IV was expressed in AbdSc AT and omental AT with relative DPP-IV mRNA expression lower in AbdSc AT taken from obese [77 ± 6 signal units (SU)] vs. lean subjects (186 ± 29 SU*, n = 10). Y1 was predominantly expressed in fat and present in all fat depots but higher in obese subjects, particularly the AbdSc AT-depot (obese: 1944 ± 111 SU vs. lean: 711 ± 112 SU**, n = 10). NPY appears to be regulated by AT-derived DPP-IV. DPP-IV inhibitors augment the antilipolytic effect of NPY in AT. Further studies are required to show whether this explains the lack of weight loss in T2DM patients treated with DPP-IV inhibitors. [ABSTRACT FROM AUTHOR]

Aim: In premenopausal women, hyperandrogenicity is associated with central obesity and an increased cardiovascular risk. The aim of this study was to investigate the effects of dydrogesterone (DYD) (a non-androgenic progestogen) and norethisterone (NET) (an androgenic progestogen) on lipoprotein lipase (LPL), hormone-sensitive lipase (HSL) and glycerol release in adipocytes isolated from subcutaneous abdominal adipose tissue. Methods: Adipose tissue was obtained from 12 non-diabetic women, mean age 51 years (range 37–78) and mean body mass index 25.4 kg/m2 (range 20.3–26.4). Adipocytes were treated with increasing doses of DYD and NET for 48 h prior to protein extraction. Effects on lipogenesis and lipolysis were assessed using western blotting to determine the expression of key enzymes, LPL (56 kDa) and HSL (84 kDa) respectively. Measurement of glycerol release into the medium provided an assessment of lipolytic activity. Results: Expression of LPL was increased by DYD and NET (mean protein expression relative to control ± s.e.), with greatest effect at 10−8 M for DYD: 2.32 ± 0.51 (p < 0.01) and 10−8 M for NET: 2.06 ± 0.19 (p < 0.01). In contrast, HSL expression was reduced by all concentrations of DYD, with maximal effect at 10−9 M : 0.49 ± 0.02 (p < 0.001). NET reduced HSL expression at all concentrations from 10−9 M : 0.62 ± 0.06 (p < 0.001) to 10−7 M : 0.69 ± 0.08 (p < 0.001). Glycerol measurements supported the HSL expression studies although they were not statistically significant (p > 0.05). Conclusions: DYD and NET significantly increased LPL expression relative to control, while significantly reducing HSL expression. At the concentrations studied, similar effects were observed with the androgenic NET and the non-androgenic DYD despite differing effects on the lipid profile when taken orally in combination with oestrogen. Further work examining the effects of different progestogens on body fat distribution may enable progestogen use to be tailored to maximize benefits and minimize potential harm. [ABSTRACT FROM AUTHOR]

Aims: Adiponectin is a 30-kDa protein secreted by adipose tissue. The aim of the present study was to compare serum adiponectin in male Indo-Asian and Caucasian subjects and examine its association with fat topography and metabolic parameters. Methods: Diabetic and non-diabetic male subjects (n = 48) were studied. A single observer carried out blood pressure and anthropometric measurements. Serum glucose, insulin, lipid profile and adiponectin (measured by RIA) were measured on a fasting sample. Results: There was no statistically significant difference in serum adiponectin between diabetic and BMI-matched non-diabetic subjects. However, serum adiponectin was lower in Indo-Asians compared with BMI-matched Caucasians, [median adiponectin (interquartile range) 3.3 (2.1–3.9) vs. 4.9 (3.5–6.6) μg/ml respectively (p = 0.016)]. Univariate analysis showed serum adiponectin to be positively associated with HDL in diabetic (p = 0.039) and non-diabetic subjects (p = 0.0098). Waist circumference (p = 0.02), saggital diameter (p = 0.04) were negatively correlated with serum adiponectin in diabetic subjects. Multiple regression analysis including waist, HDL, fasting insulin, age, diabetes and ethnicity in all subjects showed HDL to be the best predictor of serum adiponectin. Conclusions: Serum adiponectin is associated with HDL cholesterol and central obesity. Caucasians have higher serum adiponectin levels compared with Indo-Asians. Further studies are needed to explore basis for the association of adiponectin with HDL cholesterol and the reason for lower levels in Indo-Asians. [ABSTRACT FROM AUTHOR]

SUMMARY Aim To examine the expression of oestrogen receptors α and β (ERα and ERβ) and their regulation by 17β-oestradiol (E2) in stromal cells and adipocytes from human subcutaneous (s.c.) and omental (o.m.) adipose tissue. Methods Subcutaneous and o.m. abdominal adipose tissues were obtained from 10 women (mean age 63.5 ± 4.8 years; mean weight 75.6 ± 6.7 kg) undergoing elective or cosmetic surgery. Immunohistochemistry and RT-PCR analysis were used to detect the presence of ERα and ERβ. The regulation of ERα and ERβ by E2 (10-7 M to 10-9 M) was examined using Western immunoblotting analysis in both s.c. and o.m. stromal cells and mature adipocytes cultured in serum-free, phenol red-free medium. Results Immunostaining of s.c. and o.m. adipose tissue showed that the ER subtypes were localized predominantly within the nucleus. Western analysis demonstrated that E2 treatments differentially altered ERα and ERβ expression in s.c. and o.m. adipocytes. In s.c. and o.m. stromal cells, E2 (10-8 M) produced a significant up regulation relative to control of 66 kDa ERα (s.c.:1.87 ± 0.22; o.m.:1.97 ± 0.17; p < 0.05) and 60 kDa ERβ (s.c.:1.66 ± 0.3; o.m.: 1.68 ± 0.16; p < 0.05). In s.c. adipocytes, however, ERα expression significantly decreased with E2 10-8 M relative to control while ERβ expression increased (ERα 0.58 ± 0.06, ERβ: 1.47 ± 0.11; p < 0.05). In o.m. adipocytes, the inhibition of ERα with E2 was not observed (ERα 1.86 ± 0.36, ERβ:1.03 ± 0.15, p < 0.05) Conclusions ERα and ERβ are expressed but differentially regulated by E2 in s.c. and o.m. adipocytes and stromal cells. The upregulation of ERβ by E2 suggests that E2 maintains the expression of these receptors. The feed-back inhibition of ERα expression by E2 in s.c. but not o.m. adipocytes observed in vitro is consistent with the data from ERα knock out mice where s.c. fat is increased. Selective ER modulators may have different effects in different adipose sites. [ABSTRACT FROM AUTHOR]